Acquired immunodeficiency syndrome (AIDS) is caused by a virus which has at various times been called human T-cell lymphotropic virus type III (HTLV-III), or lymphadenopathy-associated virus (LAV). The virus is currently known as human immunodeficiency virus type 1 (HIV-1).
HIV-1 damages the immune system by infecting and depleting T helper/inducer lymphocytes (hereinafter referred to as "T cells"). T cells are essential because they control the production of antibodies by the B cells, the maturation of cytotoxic T lymphocytes (killer T cells), the maturation and activity of macrophages and natural killer cells, and directly and indirectly, numerous other regulator and effector functions of the immune system.
Infection of a T cell occurs through interaction between an epitope borne by HIV-1 and a receptor site which is located on the T cell surface. This receptor site on the T cell is a protein molecule known as the CD4 antigen. The epitope on HIV-1 is borne by the external envelope glycoprotein gp120 (molecular weight about 120,000 daltons).
The glycoprotein gp120 is produced when a precursor glycoprotein gp 160, made in the HIV-1-infected T cell, is cleaved apart into a transmembrane portion gp41 (molecular weight about 41,000 daltons) and gp120. Glycoprotein gp41 spans through the membrane lipid bilayer of the vizions and of the infected cells and its exterior portion is associated with gp120 through noncovalent binding. Glycoprotein gp120 bears a site which fuses with target cells, whereby the genetic material of the virus enters the cell.
Since the CD4 antigen was identified as the cell-surface receptor for HIV-1, it has been repeatedly shown that soluble forms of CD4 antigen (sCD4) can block the infectivity of the virus. Soluble CD4 inhibits diverse variants of HIV-1, indicating that all these viruses may share a relatively conserved CD4-binding region. Lasky et al. have identified a gp120-specific murine monoclonal antibody (Mab) capable of inhibiting the interaction between gp120 and CD4. Cell, 50:995-985 (1987).
The epitope recognized by this Mab has been mapped to a conserved region within amino acid residues 413-456 (numbered according to Human Retroviruses and AIDS, Los Alamos National Laboratories, 1990) where HIV-1 and distantly related HIV-2 share significant homology. This domain of gp120 appears to be important in binding to CD4. However, the CD4-binding region of the envelope glycoprotein gp120 does not appear to be immunogenic in HIV-1 infected persons, since there is very little antigenic cross-reactivity against envelope proteins between sera from patients infected with HIV-1 or HIV-2. Clavel, R. et al., Science, 233:343-346 (1986).